title: Hit-to-lead optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as a novel class of EP1 receptor antagonists.
abstract: We describe a medicinal chemistry approach to generate a series of 2-(1H-pyrazol-1-yl)thiazole compounds that act as selective EP1 receptor antagonists. The obtained results suggest that compound 12 provides the best EP1 receptor antagonist activity and demonstrates good oral pharmacokinetics.
authors.affiliation: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan. Electronic address: atobe.mb@om.asahi-kasei.co.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Atobe
authors.forename: Kenji
authors.initials: K
authors.lastname: Naganuma
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawanishi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Morimoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kasahara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Miyoshi
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D011720:Pyrazoles; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013844:Thiazoles
keywords: EP(1) receptor antagonist; HTS; Overactive bladder; Pyrazole; Thiazole